Visual outcomes of retinal pigment epithelium transplantation in patients with neovascular age-related macular degeneration: a systematic review and meta-analysis

To assess the efficacy and safety of retinal pigment epithelium (RPE) transplantation in the treatment of neovascular age-related macular degeneration (nAMD). We performed a comprehensive literature search in four databases from the date of inception until 17 March 2026. Studies meeting the inclusion criteria were appraised for quality and evaluated in terms of risk of bias. Postoperative visual outcomes including best-corrected visual acuity (BCVA) and multifocal electroretinograms (mfERGs), along with RPE transplantation related adverse events were analyzed. Twenty-one studies involving 462 eyes were included. A pooled analysis of 11 studies providing paired individual-level preoperative and postoperative BCVA data (106 eyes) demonstrated an improvement in BCVA following RPE transplantation (mean difference [MD] = -0.39, 95% confidence interval [CI]: -0.73 to -0.04, P = 0.0267, I 2 = 96.7%, LogMAR). The 95% prediction interval (PI) ranged from − 1.68 to 0.90. The b-wave amplitude of mfERGs also increased (MD = 5.34, 95% CI: 0.66 to 10.02, nV/deg 2 ). Subgroup analyses showed a significant improvement in the autologous RPE patch group (MD = -0.44, 95% CI: -0.87 to -0.02), but not in the allogeneic group (MD = -0.20, 95% CI: -0.75 to 0.36). Eyes treated with silicone oil tamponade showed a statistical improvement in BCVA (MD = -0.59, 95% CI: -0.99 to -0.19), whereas no statistically significant change was observed in the gas tamponade group (MD = 0.07, 95% CI: -0.03 to 0.17). In a post hoc exploratory subgroup analysis, studies published after 2010 showed significant BCVA improvement (MD = -0.80, 95% CI: -1.19 to -0.41), whereas those published before 2010 did not (MD = 0.06, 95% CI: -0.16 to 0.27). The 95% PIs for each of the three subgroup analyses crossed the null value. Sixty-one eyes (13.20%) required re-operation due to postoperative adverse events. Proliferative vitreoretinopathy (12.77%) was the most common adverse event, followed by choroidal neovascularization recurrence (7.79%) and epiretinal membrane (7.36%). RPE transplantation may potentially improve visual outcomes in nAMD. However, the current evidence is of low certainty and is limited by substantial heterogeneity and predominantly uncontrolled study designs. The pooled estimates should therefore be interpreted with caution, and further well-designed prospective controlled studies are needed to clarify its efficacy and safety.